Prognostic Factors in High-Grade Osteosarcoma of theExtremities or Trunk: An Analysis of 1,702 Patients Treatedon Neoadjuvant Cooperative Osteosarcoma Study GroupProtocols.

PURPOSE: To define prognostic factors for response and long-term outcome for a wide spectrum of osteosarcomas, extending well beyond those of the typical young patient with seemingly localized extremity disease. PATIENTS AND METHODS: A total of 1,702 consecutive newly diagnosed patients with high-grade osteosarcoma of the trunk or limbs registered into the neoadjuvant studies of the Cooperative Osteosarcoma Study Group before July 1998 were entered into an analysis of demographic, tumor-related, and treatment-related variables, response, and survival. The intended therapeutic strategy included preoperative and postoperative chemotherapy with multiple agents as well as surgery of all operable lesions. RESULTS: Axial tumor site, male sex, and a long history of symptoms were associated with poor response to chemotherapy in univariate and multivariate analysis. Actuarial 10-year overall and event-free survival rates were 59.8% and 48.9%. Among the variables assessable at diagnosis, patient age (actuarial 10-year survival ≥ 40, 41.6%; < 40, 60.2%; P = .012), tumor site (axial, 29.2%; limb, 61.7%; P < .0001), and primary metastases (yes, 26.7%; no, 64.4%; P < .0001), and for extremity osteosarcomas, also size (≥ one third, 52.5%; < one third, 66.7%; P < .0001) and location within the limb (proximal, 49.3%; other, 63.9%; P < .0001), had significant influence on outcome. Two additional important prognostic factors were treatment related: response to chemotherapy (poor, 47.2%; good, 73.4%; P < .0001) and the extent of surgery (incomplete, 14.6%; macroscopically complete, 64.8%; P < .0001). All factors except age maintained their significance in multivariate testing, with surgical remission and histologic response emerging as the key prognostic factors. CONCLUSION: Tumor site and size, primary metastases, response to chemotherapy, and surgical remission are of independent prognostic value in osteosarcoma.

[Delayed-Interval Delivery of an Extremely Preterm Twin after Abort of the First Twin and Emergency Total Cervical Occlusion at 19+1 Weeks of Gestation - a Case Report]. / Verlauf eines frühgeborenen Geminus nach totalem Muttermundsverschluss bei Spontanabort des ersten Geminus in der 19+1 Schwangerschaftswoche ­ Fallbericht und Literaturübersicht.

We report on the obstetric and neonatal course of a 34-year-old woman pregnant with twins, who presented at our clinic at 16+1 weeks of gestation with preterm premature rupture of membranes. We started intravenous antibiotic therapy with inpatient monitoring owing to the vitality and regular development of both twins, with anhydramnios in the leading twin. After a missed abortion of the leading twin at 19+1 weeks of gestation we decided on surgical intervention with assisted delivery of the aborted twin, leaving the placenta in situ with subsequent emergency total cervical occlusion. Afterwards, the single pregnancy could be continued until the 24th week of gestation. An urgent Caesarean section for early labor, premature rupture of membranes, and increasing signs of maternal infection was later performed. Overall, the postnatal course of the extremely preterm neonate was a success considering the gestational age. We conclude that the option of surgical interventions should be taken into account in similar cases in the future.

Osteosarcoma pre-diagnosed as another tumor: a report from the Cooperative Osteosarcoma Study Group (COSS).

PURPOSE: The course of osteosarcoma patients primarily treated as such has been well described. Little, however, is known about patients who were primarily treated assuming a different tumor diagnosis. METHODS: The database of the Cooperative Osteosarcoma Study Group COSS was searched (4.435 primary high-grade central osteosarcomas registered prior to 01/01/21). A different tumor entity had to have been assumed for at least one month after the initial diagnostic procedure before the correct diagnosis of osteosarcoma was finally made. Identified patients were analyzed for demographic, tumor-, and treatment-related factors as well as for survival outcomes. RESULTS: 37 patients were identified. They were a median of 19.7 (2.7-60.4) years old at first presentation and were more likely to be females than males (23:14). Bone cysts (n = 8), giant cell tumor of bone (n = 6), and osteoblastoma (n = 6) were the most frequent of 29/37 (78%) benign, chondrosarcoma and its variants (n = 6) the most frequent of 8/37 (22%) malignant original diagnoses. Tumors affected the extremities in 23 (62%), the trunk in 11 (30%), and the craniofacial bones in 3 (8%). Only one patient received systemic treatment while assuming the different diagnosis (1/37, 3%). The median time until the correct diagnosis of osteosarcoma was made was 8 months (range: 1 month-14.1 years). At that time, 6/37 (16%) presented with metastatic disease. All patients went on to receive chemotherapy, 17/37 (46%) neo-adjuvantly. Histologic response was only evaluated in 13/17 (76%) patients and was good (< 10% viable tumor) in only 4/13 (31%) patients. In 31/37 (84%) patients, a surgically complete resection of all macroscopically identified tumor manifestations could be achieved. Five-year overall and event-free survival rates at 5 years were 50.2% (standard error: 8.6%) and 42.6% (8.5%), respectively. CONCLUSION: Osteosarcoma may initially be misdiagnosed and hence subjected to inappropriate treatment including misguided surgery. Once diagnosed correctly, some of the affected patients may still be cured if finally treated according to modern osteosarcoma standards.

Urotherapist activities in caring for patients with pelvic floor disorders: a prospective single-center observational study.

PURPOSE: Patients with pelvic floor disorders are growing in number. The aim of this study is to outline the main activities of a urotherapist, an advanced nurse practitioner, in the care of patients with pelvic floor disorders and to evaluate patient satisfaction with the service urotherapists provide. METHODS: The prospective single-center observational study was carried out from July 2016 to June 2018. Parameters used to assess the urotherapist activities included the number of consultations, type of counselling, time frame of consultations and therapy and patient satisfaction. In a subgroup of 38 patients, satisfaction with the urotherapy sessions was evaluated by a questionnaire. RESULTS: Totally, 1709 patients were examined by urogynecologists. Five hundred and fourteen (30%) with chronic pelvic floor disorders were subsequently referred to a urotherapist. Of these patients, 60% were at least 65 years old. The most common pelvic floor disorders (221 patients; 43%) were an overactive bladder, recurrent urinary tract infections, chronic cystitis and pelvic pain syndrome; the second most common pelvic floor disorder was pelvic organ prolapsed (151 patients; 29%). Of the study subgroup comprising 38 patients, 32 (84%) returned the patient satisfaction questionnaire. All 32 patients specified their level of agreement with the urotherapist's professional competence, empathy, temporal availability and quality of advice as "agree to strongly agree." CONCLUSIONS: Management by a urotherapist was highly appreciated. The role of the urotherapist as a care coordinator, their level of autonomy and barriers to the implementation in primary care requires further exploration.

Evaluation of the DNA damage in lymphocytes, sperm and buccal cells of workers under environmental and occupational boron exposure conditions.

Industrial production and use of boron compounds have increased during the last decades, especially for the manufacture of borosilicate glass, fiberglass, metal alloys and flame retardants. This study was conducted in two districts of Balikesir; Bandirma and Bigadic, which geographically belong to the Marmara Region of Turkey. Bandirma is the production and exportation zone for the produced boric acid and some borates and Bigadic has the largest B deposits in Turkey. 102 male workers who were occupationally exposed to boron from Bandirma and 110 workers who were occupationally and environmentally exposed to boron from Bigadic participated to our study. In this study the DNA damage in the sperm, blood and buccal cells of 212 males was evaluated by comet and micronucleus assays. No significant increase in the DNA damage in blood, sperm and buccal cells was observed in the residents exposed to boron both occupationally and environmentally (p = 0.861) for Comet test in the sperm samples, p = 0.116 for Comet test in the lymphocyte samples, p = 0.042 for micronucleus (MN) test, p = 0.955 for binucleated cells (BN), p = 1.486 for condensed chromatin (CC), p = 0.455 for karyorrhectic cells (KHC), p = 0.541 for karyolitic cells (KLY), p = 1.057 for pyknotic cells (PHC), p = 0.331 for nuclear bud (NBUD)). No correlations were seen between blood boron levels and tail intensity values of the sperm samples, lymphocyte samples, frequencies of MN, BN, KHC, KYL, PHC and NBUD. The results of this study came to the same conclusions of the previous studies that boron does not induce DNA damage even under extreme exposure conditions.

Real-world extravascular lung water index measurements in critically ill patients : Pulse index continuous cardiac output measurements: time course analysis and association with clinical characteristics.

BACKGROUND: Pulse index continuous cardiac output (PiCCO) is used for hemodynamic assessment. This study describes real world extravascular lung water index (EVLWI) measurements at three time points and relates them to other hemodynamic parameters and mortality in critically ill patients admitted to a medical intensive care unit (ICU). METHODS: A total of 198 patients admitted to a tertiary medical university hospital between February 2004 and December 2010 were included in this retrospective analysis. Patients were admitted for various diseases such as sepsis (n = 22), myocardial infarction (n = 53), pulmonary embolism (n = 3), cardiopulmonary resuscitation (n = 15), acute heart failure (AHF; n = 21) and pneumonia (n = 25). RESULTS: Patients included in this analysis were severely ill as represented by the high simplified acute physiology score 2 (SAPS2, 42 ± 18) and acute physiology and chronic health evaluation score 2 (APACHE2' 22 ± 9). Real-world values at three time points are provided. Intra-ICU mortality rates did not differ between the EVLWI > 7 vs. the ELVWI < 7 groups (15% vs. 13%; p = 0.82) and no association between hemodynamic measurements obtained by PiCCO with long-term mortality could be shown. CONCLUSION: There were no associations of any PiCCO measurements with mortality most probably due to selection bias towards severely ill patients. Future prospective studies with predefined inclusion criteria and treatment algorithms are necessary to evaluate the value of PiCCO for prediction of mortality against simple clinical tools such as jugular venous pressure, edema and auscultation.

Boron-exposed male workers in Turkey: no change in sperm Y:X chromosome ratio and in offspring's sex ratio.

Boron-associated shifts in sex ratios at birth were suggested earlier and attributed to a decrease in Y- vs. X-bearing sperm cells. As the matter is pivotal in the discussion of reproductive toxicity of boron/borates, re-investigation in a highly borate-exposed population was required. In the present study, 304 male workers in Bandirma and Bigadic (Turkey) with different degrees of occupational and environmental exposure to boron were investigated. Boron was quantified in blood, urine and semen, and the persons were allocated to exposure groups along B blood levels. In the highest ("extreme") exposure group (n = 69), calculated mean daily boron exposures, semen boron and blood boron concentrations were 44.91 ± 18.32 mg B/day, 1643.23 ± 965.44 ng B/g semen and 553.83 ± 149.52 ng B/g blood, respectively. Overall, an association between boron exposure and Y:X sperm ratios in semen was not statistically significant (p > 0.05). Also, the mean Y:X sperm ratios in semen samples of workers allocated to the different exposure groups were statistically not different in pairwise comparisons (p > 0.05). Additionally, a boron-associated shift in sex ratio at birth towards female offspring was not visible. In essence, the present results do not support an association between boron exposure and decreased Y:X sperm ratio in males, even under extreme boron exposure conditions.

Large-Deviation Properties of Sequence Alignment of Correlated Sequences.

The significance of alignment scores of optimally aligned DNA sequences can be estimated through the score distribution of pairs of random sequences. It is necessary to obtain statistics for the relevant high-scoring tail of the distribution. For local alignments of iid drawn sequences it has already been shown that the often assumed Gumbel distribution does not hold in the distribution tail, but has to be corrected by a Gaussian factor. Real DNA sequences were observed to show long-range correlations within sequences, which are not correctly modeled by iid random sequences. In this publication the large deviation method that was used in previous studies is applied to local and global alignment of such sequences with long-range correlations. We study the distributions over the full range of the support and obtained probabilities as low as [Formula: see text]. We show that again a correction to the Gumbel distribution is necessary to study the dependence of the parameters on the correlation strength. For global alignments the Gamma distribution, which was found heuristically to be a good fit in earlier simple sampling studies, is found to be a poor fit.

Evaluation of FSH, LH, testosterone levels and semen parameters in male boron workers under extreme exposure conditions.

Boric acid and sodium borates are currently classified in the EU-CLP regulation as "toxic to reproduction" under "Category 1B", with hazard statement of H360FD. However, so far field studies on male reproduction in China and in Turkey could not confirm such boron-associated toxic effects. As validation by another independent study is still required, the present study has investigated possible boron-associated effects on male reproduction in workers (n = 212) under different boron exposure conditions. The mean daily boron exposure (DBE) and blood boron concentration of workers in the extreme exposure group (n = 98) were 47.17 ± 17.47 (7.95-106.8) mg B/day and 570.6 ± 160.1 (402.6-1100) ng B/g blood, respectively. Nevertheless, boron-associated adverse effects on semen parameters, as well as on FSH, LH and total testosterone levels were not seen, even within the extreme exposure group. With this study, a total body of evidence has accumulated that allows to conclude that male reproductive effects are not relevant to humans, under any feasible and realistic conditions of exposure to inorganic boron compounds.

Birth weights of newborns and pregnancy outcomes of environmentally boron-exposed females in Turkey.

Boric acid and sodium borates are currently classified as being toxic to reproduction under "Category 1B" with the hazard statement of "H360 FD" in the European CLP regulation. This has prompted studies on boron-mediated reprotoxic effects in male workers in boron mining areas and boric acid production plants. By contrast, studies on boron-mediated developmental effects in females are scarce. The present study was designed to fill this gap. Hundred and ninety nine females residing in Bandirma and Bigadic participated in this study investigating pregnancy outcomes. The participants constituted a study group covering blood boron from low (< 100 ng B/g blood, n = 143) to high (> 150 ng B/g blood, n = 27) concentrations. The mean blood boron concentration and the mean estimated daily boron exposure of the high exposure group was 274.58 (151.81-975.66) ng B/g blood and 24.67 (10.47-57.86) mg B/day, respectively. In spite of the high level of daily boron exposure, boron-mediated adverse effects on induced abortion, spontaneous abortion (miscarriage), stillbirth, infant death, neonatal death, early neonatal death, preterm birth, congenital anomalies, sex ratio and birth weight of newborns were not observed.

Correlation of Brown Adipose Tissue with Other Body Fat Compartments and Patient Characteristics: A Retrospective Analysis in a Large Patient Cohort Using PET/CT.

RATIONALE AND OBJECTIVES: The objective of this study was to assess the relationship of brown adipose tissue (BAT) activity with different fat compartments of the body, body mass index (BMI), outdoor temperature, thyroid-stimulating hormone (TSH) levels, blood glucose, age, and sex in a large patient population using F-18-fluordesoxyglucose positron emission tomography-computer tomography (FDG-PET/CT) scans obtained under thermoneutral conditions. MATERIALS AND METHODS: FDG-PET/CT scans of 4852 patients were retrospectively analyzed for BAT activity. The volumes of the different fat compartments visceral adipose tissue (VAT), subcutaneous adipose tissue (SCAT), and liver fat, were assessed by computed tomography. Age, sex, TSH levels, blood glucose levels, BMI, primary disease, and the outdoor temperature were determined. Multiple linear regression analyses were performed to identify independent relationships between the parameters. RESULTS: The VAT, SCAT, and liver fat content were lower in BAT-positive patients than in BAT-negative patients (each P < 0.0001). BAT-positive patients had a lower BMI (P < 0.0001) and were more often female (P < 0.0001), younger (P < 0.0001), and had higher TSH levels (P = 0.0002), whereas the outdoor temperature and the blood glucose level were not different compared to BAT-negative patients. Age, sex, VAT, and SCAT were independent factors related to BAT. CONCLUSIONS: Age, sex, and VAT are the most important determinants of BAT activity under thermoneutral conditions. VAT reflects the association between BAT activity and body fat mass more clearly than BMI. The strength of the association between VAT and BAT decreases during aging in men, but increases in women. This may indicate a different importance of BAT activity for obesity in men and in women.

cGMP-dependent protein kinase (PKG) mediates the anticontractile capacity of perivascular adipose tissue.

AIM: The aim of this study was to investigate the role of cGMP-dependent protein kinase (PKG) in mediating the anticontractile function of perivascular adipose tissue (PVAT) and whether its activation can rescue PVAT activity which is lost in an experimental model of inflammation. METHODS AND RESULTS: Contractile responses to norepinephrine were assessed using wire myography from small arterial segments obtained from PKG(-/-), PKG(+/+), adipo(-/-), and C57Bl6/J mice with and without PVAT during normal oxygenation and hypoxia. An anticontractile effect of PVAT was observed in control blood vessels. This was not present in arteries from PKG(-/-) or PKG(+/+) with inhibition of PKG signalling using DT-2/ODQ. Hypoxia-induced loss of PVAT function was rescued by ANP activation of PKG as there was no effect in blood vessels from PKG(-/-) mice or in the presence of DT-2. Solution transfer studies demonstrated that PKG was necessary for the normal paracrine effects of PVAT on smooth muscle and endothelium. PKG activation by atrial natriuretic peptide (ANP) did not restore the absent PVAT anticontractile capacity in arteries from adiponectin(-/-) mice; however, inhibition of PKG did not further abrogate this effect suggesting dysregulation of PKG signalling pathways in this model. The absence of PKG was associated with reduced adipocyte adiponectin expression. CONCLUSION: PKG plays a key role in regulating normal PVAT function both in modulating anticontractile factor release from adipocytes as well as being essential for its downstream dilator function in arterial smooth muscle.

Perivascular adipose tissue-derived adiponectin activates BK(Ca) channels to induce anticontractile responses.

This study aims to identify the potential mechanisms by which perivascular adipose tissue (PVAT) reduces tone in small arteries. Small mesenteric arteries from wild-type and large-conductance Ca(2+)-activated K(+) (BKCa) channel knockout mice were mounted on a wire myograph in the presence and absence of PVAT, and contractile responses to norepinephrine were assessed. Electrophysiology studies were performed in isolated vessels to measure changes in membrane potential produced by adiponectin. Contractile responses from wild-type mouse small arteries were significantly reduced in the presence of PVAT. This was not observed in the presence of a BKCa channel inhibitor or with nitric oxide synthase (NOS) inhibition or in BKCa or adiponectin knockout mice. Solution transfer experiments demonstrated the presence of an anticontractile factor released from PVAT. Adiponectin-induced vasorelaxation and hyperpolarization in wild-type arteries were not evident in the absence of or after inhibition of BKCa channels. PVAT from BKCa or adiponectin knockout mice failed to elicit an anticontractile response in wild-type arteries. PVAT releases adiponectin, which is an anticontractile factor. Its effect on vascular tone is mediated by activation of BKCa channels on vascular smooth muscle cells and adipocytes and by endothelial mechanisms.

Combined PET/CT for IMRT treatment planning of NSCLC: contrast-enhanced CT images for Monte Carlo dose calculation.

PURPOSE: Combined PET/CT imaging has been proposed as an integral part of radiotherapy treatment planning (TP). Contrast-enhanced CT (ceCT) images are frequently acquired as part of the PET/CT examination to support target delineation. The aim of this dosimetric planning study was to investigate the error introduced by using a ceCT for intensity modulated radiotherapy (IMRT) TP with Monte Carlo dose calculation for non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: Nine patients with NSCLC prior to chemo-RT were included in this retrospective study. For each patient non-enhanced, low-dose CT (neCT), ceCT and [(18)F]-FDG-PET emission data were acquired within a single examination. Manual contouring and TP were performed on the ceCT. An additional set of independent target volumes was auto-segmented in PET images. Dose distributions were recalculated on the neCT. Differences in dosimetric parameters were evaluated. RESULTS: Dose differences in PTV and lungs were small for all patients. The maximum difference in all PTVs when using ceCT images for dose calculation was -2.1%, whereas the mean difference was less than -1.7%. Maximum differences in the lungs ranged from -1.8% to 2.1% (mean: -0.1%). In four patients an underestimation of the maximum spinal cord dose between 2% and 3.2% was observed, but treatment plans remained clinically acceptable. CONCLUSIONS: Monte Carlo based IMRT planning for NSCLC patients using ceCT allows for correct dose calculation. A direct comparison to neCT-based treatment plans revealed only small dose differences. Therefore, ceCT-based TP is clinically safe as long as the maximum acceptable dose to organs at risk is not approached.

Accuracy of preoperative endorectal MRI in predicting extracapsular extension and influence on neurovascular bundle sparing in radical prostatectomy.

PURPOSE: To evaluate the accuracy of presurgical endorectal MRI (eMRI) for local staging before radical prostatectomy (RP) and its influence on neurovascular bundle (NVB) resection during radical prostatectomy. PATIENTS AND METHODS: A total of 385 patients with histologically proven prostate cancer (PCa) have been included in this retrospective study between 2004 and 2008. All patients underwent preoperative eMRI at 1.5 T before open RP. Staging results by eMRI were compared with the histopathological findings. The presence of positive surgical margins and extent of nerve-sparing procedure were evaluated. Subgroup analysis of low-risk group and intermediate to high-risk group based on D'Amico criteria was conducted. RESULTS: In 294 (76.4%) patients, pathological stage was correctly predicted, 69 patients (17.9%) were understaged and 22 (5.7%) overstaged. Overall sensitivity, specificity, negative and positive predictive value for predicting extracapsular extension (ECE) were 41.5, 91.8, 78.0 and 69.0%, respectively. One hundred and fifty-two (48.4%) of the patients classified as stage cT2 by eMRI underwent bilateral NVB sparing, whereas 14 (19.7%) patients with reported ECE underwent bilateral NVB sparing (P < 0.01). Overall positive surgical margin rate was 14.8%. Sensitivity of predicting ECE and positive predictive value were lower in the low-risk group than in the intermediate and high-risk group. CONCLUSIONS: eMRI is effective in predicting extracapsular extension in an intermediate to high-risk group. Preoperative eMRI in patients with low-risk criteria is not recommended as a routine assessment modality. eMRI findings did appear to influence surgical strategy as patients with imaging findings suggesting >cT2 disease were less likely to undergo NVB sparing.

Effect of MR contrast agents on quantitative accuracy of PET in combined whole-body PET/MR imaging.

PURPOSE: Clinical PET/MR acquisition protocols entail the use of MR contrast agents (MRCA) that could potentially affect PET quantification following MR-based attenuation correction (AC). We assessed the effect of oral and intravenous (IV) MRCA on PET quantification in PET/MR imaging. METHODS: We employed two MRCA: Lumirem (oral) and Gadovist (IV). First, we determined their reference PET attenuation values using a PET transmission scan (ECAT-EXACT HR+, Siemens) and a CT scan (PET/CT Biograph 16 HI-REZ, Siemens). Second, we evaluated the attenuation of PET signals in the presence of MRCA. Phantoms were filled with clinically relevant concentrations of MRCA in a background of water and (18)F-fluoride, and imaged using a PET/CT scanner (Biograph 16 HI-REZ, Siemens) and a PET/MR scanner (Biograph mMR, Siemens). Third, we investigated the effect of clinically relevant volumes of MRCA on MR-based AC using human pilot data: a patient study employing Gadovist (IV) and a volunteer study employing two different oral MRCA (Lumirem and pineapple juice). MR-based attenuation maps were calculated following Dixon-based fat-water segmentation and an external atlas-based and pattern recognition (AT&PR) algorithm. RESULTS: IV and oral MRCA in clinically relevant concentrations were found to have PET attenuation values similar to those of water. The phantom experiments showed that under clinical conditions IV and oral MRCA did not yield additional attenuation of PET emission signals. Patient scans showed that PET attenuation maps are not biased after the administration of IV MRCA but may be biased, however, after ingestion of iron oxide-based oral MRCA when segmentation-based AC algorithms are used. Alternative AC algorithms, such as AT&PR, or alternative oral contrast agents, such as pineapple juice, can yield unbiased attenuation maps. CONCLUSION: In clinical PET/MR scenarios MRCA are not expected to lead to markedly increased attenuation of the PET emission signals. MR-based attenuation maps may be biased by oral iron oxide-based MRCA unless advanced AC algorithms are used.

MR/PET: a new challenge in hybrid imaging.

OBJECTIVE: This article provides a short overview of hybrid imaging and the potential advantages of combined MR/PET. We will address some of the challenges that had to be met before MR/PET could become clinically available as well as further scientific work that has to be done to increase the potential benefit of this emerging hybrid modality. CONCLUSION: Hybrid imaging, the combination of two imaging modalities into one, promises the compensation of specific deficits of the modalities involved. PET/CT has gained wide acceptance for oncologic imaging in recent years; however, MRI has certain advantages that could make combined MR/PET more tempting in various clinical applications. The development of new clinical whole-body MR/PET systems offers new insights in metabolic and functional processes in oncology as well as cardiovascular and neurologic diseases.

Condylar metastasis from prostatic carcinoma mimicking temporomandibular disorder: a case report.

BACKGROUND: Although metastatic carcinoma is the most common malignant tumor of the bone, less than 1% of all metastatic bone lesions are presented in the maxillofacial area. As the mandibular body is the most frequent localization, metastasis to the mandibular condyle is extremely rare. CASE REPORT: This report describes a rare case of prostate carcinoma metastatic to the mandibular condyle in a 75-year old man, who was referred because of persistent pain in the temporomandibular joint (TMJ) region and a limitation of opening, initially misdiagnosed and treated as temporomandibular disorder (TMD). Histopathological examination confirmed the suspected metastasis of prostate carcinoma and local radiation therapy was performed. DISCUSSION: TMD represent a diagnostic challenge and sometimes an interdisciplinary approach is required to prevent a delay of the correct treatment. Metastatic cancer should be included in the differential diagnosis of TMD, especially in patients with a malignant disease.

Amplified NO/cGMP-mediated relaxation and ryanodine receptor-to-BKCa channel signalling in corpus cavernosum smooth muscle from phospholamban knockout mice.

BACKGROUND AND PURPOSE: Relaxation of corpus cavernosum smooth muscle (CCSM) is induced by NO. NO promotes the formation of cGMP, which activates cGMP-dependent protein kinase I (PKGI). The large conductance calcium-activated potassium (BK(Ca) ) channel is regarded as a major target of NO/cGMP signalling; however, the mechanism of BK(Ca) activation remains unclear. The aim of the present study was to determine whether sarcoplasmic reticulum (SR) Ca(2+) load and Ca(2+) release from the SR via ryanodine receptors (RyRs) is important for BK(Ca) channel activation in response to NO/cGMP. EXPERIMENTAL APPROACH: In vitro myography was performed on CCSM strips from wild-type and PLB knockout (PLB(-/-)) mice to evaluate contraction and relaxation in response to pharmacological agents and electrical field stimulation (EFS). KEY RESULTS: In CCSM strips from PLB(-/-) mice, a model of increased SR Ca(2+) load, contractile force in response to EFS or phenylephrine (PE) was increased by nearly 100%. EFS of strips precontracted with PE induced transient relaxation in CCSM, an effect that was significantly larger in PLB(-/-) strips. Likewise, the relaxation of PE-induced contraction in response to SNP and cGMP was greater in PLB(-/-) , as demonstrated by a shift in the concentration-response curve towards lower concentrations. Blocking RyRs and BK(Ca) channels diminished the induced relaxations and eliminated the difference between wild-type and PLB(-/-). CONCLUSIONS AND IMPLICATIONS: NO/cGMP activates BK(Ca) channels through RyR-mediated Ca(2+) release. This signalling pathway is responsible for approximately 40% of the NO/cGMP effects and is amplified by increased SR Ca(2+) concentrations.

Nonspecific FDG uptake in the tongue mimicking the primary tumor in a patient with cancer of unknown primary.

For cancers of the head and neck, the combination of (18)F-fluorodeoxy-glucose positron emission tomography (FDG-PET)/computed tomography (CT) gains wide acceptance, especially if the primary tumor is unknown (CUP). A patient underwent FDG-PET/CT for squamous cell CUP with cervical lymph node metastases. FDG-PET/CT showed uptake in the right side of the tongue, rendering this area a possible location for the primary tumor. However, clinical examination revealed a deviation of the tongue toward the left side indicating affection of the left hypoglossal nerve, causing the increased FDG uptake. This case illustrates the interpretive pitfalls of unspecific FDG uptake in PET/CT imaging of the head and neck.